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Guillaume Achaz

Publications and source records attributed to Guillaume Achaz.

4 recordsLinked to original sources

Accuracy of demographic inferences from Site Frequency Spectrum: The case of the Yoruba population

Some methods for demographic inference based on the observed genetic diversity of current populations rely on the use of summary statistics such as the Site Frequency Spectrum (SFS). Demographic models can be either model-constrained with numerous parameters such as growth rates, timing of demographic events and migration rates, or model-flexible, with an unbounded collection of piecewise constant sizes. It is still debated whether demographic histories can be accurately inferred based on the SFS. Here we illustrate this theoretical issue on an example of demographic inference for an African population. The SFS of the Yoruba population (data from the 1000 Genomes Project) is fit to a simple model of population growth described with a single parameter (e.g., founding time). We infer a time to the most recent common ancestor of 1.7 million years for this population. However, we show that the Yoruba SFS is not informative enough to discriminate between several different models of growth. We also show that for such simple demographies, the fit of one-parameter models outperforms the model-flexible method recently developed by Liu and Fu. The use of this method on simulated data suggests that it is biased by the noise intrinsically present in the data.

Evolutionary Biology

Measuring epistasis in fitness landscapes: the correlation of fitness effects of mutations

Genotypic fitness landscapes are constructed by assessing the fitness of all possible combinations of a given number of mutations. In the last years, several experimental fitness landscapes have been completely resolved. As fitness landscapes are high-dimensional, simple measures of their structure are used as statistics in empirical applications. Epistasis is one of the most relevant features of fitness landscapes. Here we propose a new natural measure of the amount of epistasis based on the correlation of fitness effects of mutations. This measure has a natural interpretation, captures well the interaction between mutations and can be obtained analytically for most landscape models. We discuss how this measure is related to previous measures of epistasis (number of peaks, roughness/slope, fraction of sign epistasis, Fourier-Walsh spectrum) and how it can be easily extended to landscapes with missing data or with fitness ranks only. Furthermore, the dependence of the correlation of fitness effects on mutational distance contains interesting information about the patterns of epistasis. This dependence can be used to uncover the amount and nature of epistatic interactions in a landscape or to discriminate between different landscape models.

Evolutionary Biology

Decomposing the site frequency spectrum: the impact of tree topology on neutrality tests

We investigate the dependence of the site frequency spectrum (SFS) on the topological structure of genealogical trees. We show that basic population genetic statistics - for instance estimators of{theta} or neutrality tests such as Tajimas D - can be decomposed into components of waiting times between coalescent events and of tree topology. Our results clarify the relative impact of the two components on these statistics. We provide a rigorous interpretation of positive or negative values of an important class of neutrality tests in terms of the underlying tree shape. In particular, we show that values of Tajimas D and Fay and Wus H depend in a direct way on a peculiar measure of tree balance which is mostly determined by the root balance of the tree. We present a new test for selection in the same class as Fay and Wus H and discuss its interpretation and power. Finally, we determine the trees corresponding to extreme expected values of these neutrality tests and present formulae for these extreme values as a function of sample size and number of segregating sites.

Genetics

MAGELLAN: a tool to explore small fitness landscapes

1In a fitness landscape, fitness values are associated to all genotypes corresponding to several, potentially all, combinations of a set of mutations. In the last decade, many small experimental fitness landscapes have been partially or completely resolved, and more will likely follow. MAGELLAN is a web-based graphical software to explore small fitness/energy landscapes through dynamic visualization and quantitative measures. It can be used to explore input custom landscapes, previously published experimental landscapes or randomly generated model landscapes.

Evolutionary Biology